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Susumu Tonegawa
Learning and memory are vital for day-to-day living, from finding our way home to playing tennis to making a cohesive speech. Many of us have personally witnessed the devastating consequences of memory disorders such as Alzheimer's and Parkinson's diseases. The main research interest of Professor Susumu Tonegawa's lab is to understand the molecular, cellular, neuronal circuitry, and neural systems mechanisms underlying learning and memory and associated cognitive functions.
Our main approach is to generate conditionally engineered mouse strains in which a specific gene or its protein function is eliminated in a spatially restricted and/or temporally controlled manner in the brain; we then analyze these mice with a series of techniques designed to detect abnormal phenotypes at different levels of complexity from molecules and cells to neuronal circuitries and brain systems to behavior of a whole living animal. These techniques include those of molecular and cell biology, histology and histochemistry, confocal and two-photon laser microscopy, in vitro and in vivo electrophysiology, and behavioral studies. Our goal is to identify a correlate at a particular level of complexity of an event occurring at another level, and eventually establish their cause-consequence relationship from molecules all the way to behavior.
As research targets, we have thus far focused on hippocampus-dependent memory, i.e., memory of events, facts, space, etc. The hippocampus consists of multiple interconnected areas such as area CA1, CA3 and the dentate gyrus (DG), each of which contains a unique set of neurons composing a distinct cellular network. We aim to identify the roles of specific proteins (e.g., NMDA receptors), synaptic plasticity and neural circuitries in each of these areas in different stages of the mnemonic process such as memory acquisition, consolidation and recall. For instance, we have recently demonstrated that NMDA receptors in a neural circuit in CA3 play a crucial role in both rapid acquisition and recall of an episodic memory.
Another important development in the lab was the identification of a gene (calcinearine) whose variation increased susceptibility to schizophrenia. This discovery was made by combining the behavioral analysis of a genetically engineered mouse and genetic analysis of DNA from human schizophrenia patients.
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